Rational design of biologically active peptides: inhibition of T cell activation through interference with CD4 function (vol 13, pg S306, 2000)

In our laboratory we generated one synthetic cyclic peptide (Pep4) and test ed it in human mitogen stimulation assays (MSA) and mixed lymphocytes react ions (MLR) generating dose-response curves showing a dose-dependent inhibit ion of MSA up to 80 % and MLR up to 98 %. MSA and MLR were repeated after p re incubation of the Pep4 with each separate responder cell subset and subs equent reconstitution: these experiments showed inhibition only when the pe ptide was present in culture. Pep4 showed species specificity since it was ineffective in inhibiting rat MLR. Combination effect analysis with Pep4 an d cyclosporine showed a combination index > 1. This rationally designed pep tide (Pep4) shows powerful inhibition of human T cell activation and, altho ugh the exact mechanism is still undefined, it seems to exert its major act ion on the T cell surface, interfering with co receptor interaction and dis rupting the same activation signal pathway inhibited by cyclosporine A.